IL-4 signaling in human coronary artery endothelial cells

IL-4 signalling is critically involved in Th2 driven allergic inflammatory responses. IL-4 generates a proinflammatory enviornment and may cause barrier dysfunction in vascular endothelial cells (VECs). However, the effectors responsible for IL-4 induced barrier dysfunction in adult human VECs still remain unclear. Here we show that IL-4 upregulates the expression of Wnt5A which can mediate cytoskeleton remodeling in VECs. We further show that IL-4 induced cytoskeleton remodeling involving stress fiber formation can be decreased by antagonizing Wnt5A. Further we demonstrate that silencing Wnt5A significantly improves the barrier function of IL-4 treated endothelial monolayer. Additionally, we rule out the involvement of IL-6 in IL-4 induced barrier dysfunction of VECs. These findings suggest a critical role for Wnt5A in mediating IL-4 induced endothelial barrier dysfunction and edem formation in Th2 driven inflammatory diseases. A two color competitive hybridization design was chosen. Samples from respective treatments are labelled with Cy5 and hybridized against a Cy3 labelled non-treated reference sample from the same experiment.